Enhancing excitatory activity of somatosensory cortex alleviates neuropathic pain through regulating homeostatic plasticity

摘要: Central sensitization and network hyperexcitability of the nociceptive system is a basic mechanism neuropathic pain. We hypothesize that development cortical underlying pain may involve homeostatic plasticity in response to lesion-induced somatosensory deprivation activity loss, can be controlled by enhancing activity. In mouse model pain, vivo two-photon imaging patch clamp recording showed initial loss subsequent recovery enhancement spontaneous firings pyramidal neurons. Unilateral optogenetic stimulation neurons both prevented reduced pain-like behavior as detected bilateral mechanical hypersensitivity hindlimbs, but corpus callosotomy eliminated analgesic effect was ipsilateral, not contralateral, stimulation, suggesting involvement inter-hemispheric excitatory drive this effect. Enhancing focally blocking GABAergic inhibition had similar relieving on behavior. Patch recordings from layer V normalized through changing neuronal membrane properties reducing frequency postsynaptic events. conclude involves abnormal regulation cortex, novel strategy for preventing controlling